NCT06636227

Diclofenac Dose Response Study

Recruiting now Phase 1 Last updated 9 February 2026

What this trial tests

Phase 1 trial testing Diclofenac 100mg in Alcohol Use Disorder (AUD) in 24 participants. Currently enrolling.

Timeline

1 December 2024

Primary endpoint
31 May 2026

31 August 2026

Quick facts

Lead sponsor	University of Maryland, Baltimore
Phase	Phase 1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	quadruple
Primary purpose	treatment
Enrollment	24
Start date	1 December 2024
Primary completion	31 May 2026
Estimated completion	31 August 2026
Sites	1 location across United States

Drugs / interventions tested

• Diclofenac 100mg — full drug profile →
• Diclofenac 75mg — full drug profile →
• Diclofenac 50mg — full drug profile →
• Placebo control

Conditions studied

• Alcohol Use Disorder (AUD) — all drugs for Alcohol Use Disorder (AUD) →
• Alcohol-Related Disorders — all drugs for Alcohol-Related Disorders →

Sponsor

University of Maryland, Baltimore

Who can join

Adults 21 to 65, any sex, with Alcohol Use Disorder (AUD) or Alcohol-Related Disorders. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The development of efficacious medications for AUD remains a high research priority with current emphases on identifying novel molecular targets and efficiently screening new compounds. Pharmacological modulation of the kynurenine pathway (KP) represents a promising novel target for AUD. The KP is a complex enzymatic cascade with each step producing biologically active metabolites that are critically involved in diverse physiological and pathological processes. Chronic alcohol exposure produces dysregulation of the KP, particularly as evidenced by decreased levels of the neuroprotective metabolite kynurenic acid (KYNA) and increased levels of the neurotoxic metabolite quinolinic acid (QUIN). This metabolic shift is associated with various alcohol-related pathologies in animals and humans. Thus, a medication that targets the KP to restore KYNA and attenuate QUIN levels may be an effective treatment for AUD. The enzyme kynurenine 3- monooxygenase (KMO) is a major gatekeeper of the KP and resultant KYNA levels. KMO inhibition shifts the KP towards KYNA production in brain and away from QUIN production. Critically, KMO inhibition in rodents, through its increase in brain KYNA levels, decreases alcohol self-administration, preference, cue-reactivity, and relapse behaviors. However, KMO-inhibitors have not been tested in humans because of presumed lack of availability. Diclofenac is an FDA-approved Non-Steroidal Anti-Inflammatory Drug that was recently discovered to inhibit KMO activity. Consistent with KMO inhibition, diclofenac increases KYNA levels in the brain and periphery of rodents. However, it remains unknown whether diclofenac increases KYNA levels and affects alcohol-related behaviors in humans at approved, safe dosages.

Investigators propose to conduct a human laboratory pilot study to test whether diclofenac can increase KYNA in individuals with AUD, and if so, which of 3 doses (50, 75, or 100 mg) most effectively increases KYNA. Individuals with AUD (n = 24) will complete four sessions where they receive diclofenac (50, 75, or 100 mg) or placebo. Investigators will examine increases in KYA levels and will also assess QUIN levels, alcohol craving, and negative mood.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Pharmacological interventions for alcohol use disorder: novel insights from recent clinical trials.
   McManus KR, Ray LA. · · 2026 · PMID 41611606 · DOI 10.1080/17512433.2026.2625341